Nicotianamine (NA) is a non-proteinogenic amino acid present in all higher plants. In vitro, NA can chelate many metal ions (Fe, Mn, Zn, Ni, Cu) and, in vivo, it plays an important role in the homeostasis of these metals in plants.
In addition, it has been shown that nicotianamine has antihypertensive properties through the inhibition of angiotensin I-converting enzyme (ACE) (Kinoshita et al., Biosci Biotechnol Biochem, 57, 1107-10, 1993; Shimizu et al., J Nutr Sci Vitaminol (Tokyo), 45, 375-83, 1999; Wada et al., Biosci Biotechnol Biochem, 70, 1408-15, 2006).
In higher plants, nicotianamine biosynthesis is catalyzed by the nicotianamine synthase (NAS; EC 2.5.1.43) and is the result of the trimerization of three S-adenosyl methionine (SAM) molecules. Sequence database searches have made it possible to detect putative homologs of NAS in organisms other than higher plants, in particular in fungi and archaea (Trampczynska et al., FEES Lett, 580, 3173-8, 2006; Herbik et al., Eur J Biochem, 265, 231-9, 1999). The presence of a functional NAS has also been demonstrated in the filamentous fungus Neurospora crassa (Trampczynska et al., FEBS Lett, 580, 3173-8, 2006). Recently, the team of the inventors (Dreyfus et al., Acta Cryst., F64, 933-5, 2008) has expressed, in E. coli, an enzyme of the archaeon Methanothermobacter thermoautotrophicus (MTH675; GenBank NP—275817), which is a homolog of eukaryotic NASs. This enzyme will hereinafter be referred to as MtNAS.